Daily Rhythmic Behaviors and Thermoregulatory Patterns Are Disrupted in Adult Female MeCP2-Deficient Mice

Mutations in the X-linked gene encoding Methyl-CpG-binding protein 2 (MECP2) have been associated with neurodevelopmental and neuropsychiatric disorders including Rett Syndrome, X-linked mental retardation syndrome, severe neonatal encephalopathy, and Angelman syndrome. Although alterations in the performance of MeCP2-deficient mice in specific behavioral tasks have been documented, it remains unclear whether or not MeCP2 dysfunction affects patterns of periodic behavioral and electroencephalographic (EEG) activity. The aim of the current study was therefore to determine whether a deficiency in MeCP2 is sufficient to alter the normal daily rhythmic patterns of core body temperature, gross motor activity and cortical delta power. To address this, we monitored individual wild-type and MeCP2-deficient mice in their home cage environment via telemetric recording over 24 hour cycles. Our results show that the normal daily rhythmic behavioral patterning of cortical delta wave activity, core body temperature and mobility are disrupted in one-year old female MeCP2-deficient mice. Moreover, female MeCP2-deficient mice display diminished overall motor activity, lower average core body temperature, and significantly greater body temperature fluctuation than wild-type mice in their home-cage environment. Finally, we show that the epileptiform discharge activity in female MeCP2-deficient mice is more predominant during times of behavioral activity compared to inactivity. Collectively, these results indicate that MeCP2 deficiency is sufficient to disrupt the normal patterning of daily biological rhythmic activities.编码甲基CpG结合蛋白2（Methyl-CpG-binding protein 2, MECP2）的X连锁基因发生突变，已被证实与多种神经发育及神经精神疾病相关，包括雷特综合征（Rett Syndrome）、X连锁智力障碍综合征、重度新生儿脑病以及安格尔曼综合征（Angelman syndrome）。尽管已有文献报道MeCP2缺陷小鼠在特定行为任务中存在表现异常，但目前仍不清楚MeCP2功能异常是否会影响周期性行为与脑电图（electroencephalographic, EEG）活动的模式。因此本研究旨在探究MeCP2缺陷是否足以改变核心体温、大运动活动以及皮层δ波功率的正常日常节律模式。为解答这一科学问题，我们通过遥测记录技术，在24小时周期内于小鼠的笼养环境中对野生型与MeCP2缺陷型小鼠个体进行了持续监测。研究结果显示，一岁龄雌性MeCP2缺陷小鼠的皮层δ波活动、核心体温与运动能力的正常日常节律行为模式均遭到破坏。此外，与野生型小鼠相比，笼养环境下的雌性MeCP2缺陷型小鼠整体运动活动减弱、平均核心体温更低，且体温波动幅度显著更大。最后，我们发现雌性MeCP2缺陷小鼠的癫痫样放电活动在行为活跃时段较静息时段更为显著。综上，上述结果表明MeCP2缺陷足以破坏日常生物节律活动的正常模式。